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H Xie

Publications and source records attributed to H Xie.

At least 145 records · Page 8Linked to original sources

In vivo function of mutated spliced leader RNAs in Caenorhabditis elegans.

The role of spliced leader RNA (SL RNA) in trans-splicing in Caenorhabditis elegans has been studied through a combination of in vitro mutagenesis and in vivo complementation of rrs-1 mutant nematodes, which lack endogenous SL1 RNA. Three classes of mutant SL1 RNAs have been found-those that rescue the lethal phenotype at low concentration of transforming DNA, those that rescue at high but not low concentration, and those that do not rescue at all. These studies showed that some mutations in the otherwise highly conserved 22-nt spliced leader are tolerated for splicing and post-splicing events. A longer spliced leader also can be tolerated but only when present in high copy number. Changes in the first 16 nucleotides result in the appearance of no SL RNA, consistent with the in vitro studies by others showing that the SL1 RNA promoter partly resides within the spliced leader sequence.

Animals↗

MR image-guided portal verification for brain treatment field.

PURPOSE: To investigate a method for the generation of digitally reconstructed radiographs directly from MR images (DRR-MRI) to guide a computerized portal verification procedure. METHODS AND MATERIALS: Several major steps were developed to perform an MR image-guided portal verification procedure. Initially, a wavelet-based multiresolution adaptive thresholding method was used to segment the skin slice-by-slice in MR brain axial images. Some selected anatomical structures, such as target volume and critical organs, were then manually identified and were reassigned to relatively higher intensities. Interslice information was interpolated with a directional method to achieve comparable display resolution in three dimensions. Next, a ray-tracing method was used to generate a DRR-MRI image at the planned treatment position, and the ray tracing was simply performed on summation of voxels along the ray. The skin and its relative positions were also projected to the DRR-MRI and were used to guide the search of similar features in the portal image. A Canny edge detector was used to enhance the brain contour in both portal and simulation images. The skin in the brain portal image was then extracted using a knowledge-based searching technique. Finally, a Chamfer matching technique was used to correlate features between DRR-MRI and portal image. RESULTS: The MR image-guided portal verification method was evaluated using a brain phantom case and a clinical patient case. Both DRR-CT and DRR-MRI were generated using CT and MR phantom images with the same beam orientation and then compared. The matching result indicated that the maximum deviation of internal structures was less than 1 mm. The segmented results for brain MR slice images indicated that a wavelet-based image segmentation technique provided a reasonable estimation for the brain skin. For the clinical patient case with a given portal field, the MR image-guided verification method provided an excellent match between features in both DRR-MRI and portal image. Moreover, target volume could be accurately visualized in the DRR-MRI and mapped over to the corresponding portal image for treatment verification. The accuracy of DRR-MRI was also examined by comparing it to the corresponding simulation image. The matching results indicated that the maximum deviation of anatomical features was less than 2.5 mm. CONCLUSION: A method for MR image-guided portal verification of brain treatment field was developed. Although the radiographic appearance in the DRR-MRI is different from that in the portal image, DRR-MRI provides essential anatomical features (landmarks and target volume) as well as their relative locations to be used as references for computerized portal verification.

Brain Neoplasms↗

Hyperbaric oxygen and basic fibroblast growth factor promote growth of irradiated bone.

PURPOSE: The goal of the current experiment is to test for protective effect of hyperbaric oxygen (HBO) and basic fibroblast growth factor (bFGF) on bone growth. METHODS AND MATERIALS: Control C3H mice received hind leg irradiation at 0, 10, 20, or 30 Gy. HBO-treated groups received radiation 1, 5, or 9 weeks before beginning HBO. The remaining groups began bFGF +/- HBO 1 or 5 weeks after 30 Gy. HBO treatments were given 5 days per week for 4 weeks at 2 ATA for 3 h/day. bFGF was given intravenously at 6 microg twice a week for 4 weeks. RESULTS: HBO improved bone growth after radiation in the 10 and 20 Gy groups. At 18 weeks control tibia length discrepancy is 0.0, 4.2, 8.2, and 10.7% after 0, 10, 20, and 30 Gy, respectively. HBO beginning in week 1, 5, or 9 following 10 Gy decreased these discrepancies to 2.0% (p < 0.05), 1.8% (p < 0.05), and 2.4% (p < 0.05), respectively. After 20 Gy, HBO decreased these discrepancies to 7.0% (p = ns), 4.9% (p < 0.05), and 3.6% (p < 0.05), respectively. At 30 Gy, HBO alone had no effect on bone shortening. bFGF improved tibia length discrepancy with or without HBO. At 18 weeks length discrepancies were 6.5% (p < 0.05) and 7.3 (p < 0.05), and after bFGF alone were 6.8% (p < 0.05) and 7.3% (p < 0.05) for treatment beginning in week 1 or 5, respectively. Tibial growth at 18 and 33 weeks following radiation were similar. CONCLUSION: Radiation effects on bone growth can be significant reduced by HBO after 10 or 20 Gy, but not after 30 Gy. At 30 Gy bFGF still significantly reduced the degree of bone shortening, but HBO provided no added benefit to bFGF therapy.

Animals↗

Benefits and costs of supported employment from three perspectives.

Administrators, consumers, and policy makers are increasingly interested in supported employment as a way of helping persons with severe mental illness get and keep competitive jobs. However, in an atmosphere of increased expectations for performance and declining public financing, administrators want to know the costs and benefits of different approaches before they reallocate scarce treatment or rehabilitative dollars. This article discusses the net benefits of two approaches to supported employment that were compared in a randomized trial: Individual Placement and Support (IPS) and Group Skills Training (GST). The authors analyze costs and benefits from societal, government, and consumer perspectives. Although a previous analysis showed that IPS participants were significantly more likely to find work, worked more hours, and had higher earnings, net benefits of the two programs were not significantly different. The authors also discuss some of the strengths and weaknesses of cost-benefit analysis in mental health care and suggest future directions for policy and research.

Adult↗

Improved long-term survival for unresectable hepatocellular carcinoma (HCC) with a combination of surgery and intrahepatic arterial infusion of 131I-anti-HCC mAb. Phase I/II clinical trials.

Resectional therapy has been accepted as the only curative therapy for hepatocellular carcinoma (HCC). Unfortunately, it is estimated that only 10% of HCC are resectable at the time of diagnosis. Cytoreduction and sequential resection offer a new hope for patients with unresectable HCC. Radioimmunotherapy (RIT) is an attractive approach for cytoreduction. We have previously shown that intrahepatic arterial 131I-labelled anti-HCC monoclonal antibody (131I-Hepama-1 mAb) could be used safely in combination with hepatic artery ligation for treatment of unresectable HCC, and encouraging results have been achieved. In this paper, the long-term survival and the prognostic factors in HCC patients treated with radioimmunotherapy will be analysed. Sixty-five patients with surgically verified unresectable HCC were treated with hepatic artery ligation plus hepatic artery cannulation and infusion from 1990 to 1992. Thirty-two patients were enrolled in a phase I-II clinical trial with infusion of 131I-radiolabelled anti-HCC monoclonal antibody (Hepama-1 mAb) via the hepatic artery (the RIT group). Another 33 patients formed the group treated with intrahepatic-arterial chemotherapy (the non-RIT group). T cell subsets were measured in 24 patients and human anti-(murine Ig) antibody (HAMA) were monitored in the RIT group. The 5-year survival rate was significantly higher in the RIT group than in the chemotherapy group, being 28.1% compared to 9.1% (P < 0.05); this was mainly a result of better cytoreduction and a higher sequential resection rate (53.1% compared to 9.1%). Significant prognostic factors in the RIT group included tumour capsule status and the number of tumour nodules. HAMA incidence and CD4+ T lymphocytes influenced short-term, but not long-term survival. It is suggested that intrahepatic-arterial RIT, using 131I-Hepama-1 mAb, combined with hepatic artery ligation might be an effective approach to improve long-term survival in some patients with unresectable HCC, which may successfully be made resectable by intra-arterial infusion of 131I-Hepama-1 mAb.

Adult↗

Yellow fever 17D vaccine virus isolated from healthy vaccinees accumulates very few mutations.

The live attenuated yellow fever (YF) vaccine strain 17D is one of the safest vaccines in use today with only 22 cases of reversion to virulence documented from over 300 million doses administered. We have isolated virus in cell culture from sera of six volunteers who received 17D vaccine and found that very few nucleotide mutations were detected in the consensus sequence of the entire genome of each of the serum viruses. Moreover, most of these mutations accumulated in the non-structural protein genes, especially the NS5 protein gene. Although no nucleotide change was identified in the structural protein genes of any of these six serum viruses, minor sequence heterogeneity existed in the serum virus population. Our results indicate that 17D vaccine virus accumulates mutations at a very low frequency and may explain in part the excellent safety record of 17D vaccine.

Amino Acid Sequence↗

Transcripts of the transposon mariner are present in epileptic brain.

Mobile genetic elements termed transposons have been increasingly implicated in human disease. The small transposon mariner is widespread within non-vertebrate genomes and causes mutation by replication, excision, and insertion of itself without an RNA intermediate. We find that human DNA contains about 60 copies of this gene. Mariner transcripts are abundant in RNA prepared from sclerotic epileptic hippocampi. In contrast, typically no mariner-specific RNA is detected in non-sclerotic hippocampi from other epileptic patients or from autopsies. A complete but non-functional copy was obtained using rapid amplification of cDNA ends (RACE). This human mariner transcript is approximately 45% homologous to a functional counterpart active in Drosophila, with a coding region of 1035 bases flanked by 32 base inverted terminal repeats. The differential expression of mariner transcripts within sclerotic hippocampi suggests the probable activity of an autonomous element which by mutating critical genes could establish an epileptogenic substrate in the hippocampus.

Amino Acid Sequence↗

Job terminations among persons with severe mental illness participating in supported employment.

For persons with psychiatric disabilities, maintaining a job is often more difficult than acquiring a job. A large proportion of jobs end unsatisfactorily. This study explored job terminations among 63 persons with severe mental illness who participated in competitive jobs through supported employment programs. More than half of the job terminations were unsatisfactory, defined as the client quitting without having other job plans or being fired. Baseline ratings of demographic and clinical characteristics, preemployment skills training, and early ratings of job satisfaction and work environment did not predict unsatisfactory terminations. Clients with better work histories were less likely to experience unsatisfactory terminations. In addition, unsatisfactory terminations were associated retrospectively with multiple problems on the job that were related to interpersonal functioning, mental illness, dissatisfaction with jobs, quality of work, medical illnesses, dependability, and substance abuse. These results suggest that supported employment programs need to address job maintenance with interventions that identify and address different types of difficulties as they arise on the job.

Adult↗

Paths across generations: academic competence and aggressive behaviors in young mothers and their children.

This research compared the social and cognitive development of young mothers when they were children with the social and cognitive development of their offspring. Intergenerational development was investigated over a 17-year period for 57 women who had been studied longitudinally from childhood to adulthood and who became young mothers (R. B. Cairns & B. D. Cairns, 1994). The children of these women, in turn, were followed prospectively from 1 to 2 years old through the early school years. The academic competence of mothers when they were children was significantly linked to the academic competence of their children at school age. In contrast, the across-generation correlations between measures of aggressive behavior of the mothers when they were children and measures of aggressive behavior of their children in early school grades were modest and unreliable. Certain within-generation continuities were observed in both cognitive and aggressive development.

Adult↗

Assertive community treatment for patients with co-occurring severe mental illness and substance use disorder: a clinical trial.

Integrated mental health and substance abuse treatment within an assertive community treatment (ACT) approach was compared to that within a standard case management approach for 223 patients with dual disorders over three years. ACT patients showed greater improvements on some measures of substance abuse and quality of life, but the groups were equivalent on most measures, including stable community days, hospital days, psychiatric symptoms, and remission of substance use disorder.

Adult↗

Methodological issues in assertive community treatment studies.

Recent evaluations of ACT programs have produced equivocal findings, often leading to the invocation of methodological problems as responsible for the lack of positive results. This paper discusses issues of theory and methodology as they pertain to improving research of ACT, with particular attention paid to issues of sampling, process evaluation, measurement, and data analysis.

Bias↗

Enhanced radioimmunotherapeutic efficacy of a monoclonal antibody cocktail against SMMC-7721 human hepatocellular carcinoma.

The improved tumoricidal effect of the radioantibody mixture ("cocktail") has been reported recently for the treatment of colon tumor. In the present study, we demonstrated the enhanced radioimmunotherapeutic efficacy of a monoclonal antibody (MAb) cocktail against human hepatocellular carcinoma. Therapeutic efficacy was determined by measuring the change in tumor size over a period, determining the percentage of growth inhibition of each treatment at various times after radioantibody therapy. Radioimmunotherapy of SMMC-7721 human hepatoma xenografts in athymic nude mice with combination of 131I-labeled Hepama-1 and 131I-labeled 9403 mouse MAbs was more effective than using either Hepeam-1 or 9403 MAb alone The MAb cocktail could target a greater number of hepatoma cells and increase the magnitude of hepatoma cell uptake of radioantibodies. The in vitro results explain the enhanced effect of the MAb cocktail in in vivo model system.

Animals↗

Expression, characterization, processing and immunogenicity of an insulin-dependent diabetes mellitus autoantigen, IA-2, in Sf-9 cells.

Autoantibodies to a 64-kD protein and a 40-kD tryptic fragment from pancreatic islets have been detected at high frequency in the sera of patients with insulin-dependent diabetes mellitus (IDDM). IA-2, a newly isolated transmembrane protein tyrosine phosphatase, is a major islet cell autoantigen in IDDM and the precursor of a 40-kD tryptic fragment. To express large quantities of recombinant IA-2 protein and analyse post-translational modifications we expressed full-length human IA-2 in baculovirus-infected Sf-9 cells. IA-2 expression was analysed by Western blot and by immunoprecipitation of 35S-methionine-radiolabelled proteins with rabbit antisera or IDDM sera. A 120-kD IA-2 protein was detected during the early, but not the late, phase of the infection. Pulse-chase experiments showed that the 120-kD protein was processed into fragments of 64 kD and smaller fragments of approximately 50 kD, 38 kD and 32 kD. The 64-kD fragment appeared as a doublet. Tunicamycin and PNGase F treatment down-shifted the 120-kD protein and the 64-kD doublet into lower molecular weight bands, suggesting that both were glycosylated. Trypsin treatment converted the 120-kD protein and the 64-kD doublet into a 40-kD fragment. Baculovirus-expressed IA-2 was as sensitive or slightly more sensitive than in vitro translated IA-2 in detecting autoantibodies to IA-2: 66% of sera from newly diagnosed IDDM patients reacted with baculovirus-expressed IA-2 compared with 59% of the same sera which reacted with in vitro translated IA-2. It is concluded that baculovirus-expressed IA-2 is a good source of autoantigen and that a number of lower molecular weight fragments with which IDDM autoantibodies react are derived from the 120-kD full-length IA-2 molecule.

Animals↗

Characterization of a novel monoclonal antibody raised against human hepatocellular carcinoma.

A monoclonal antibody (MAb) targeting human hepatocellular carcinoma (HCC) has been produced by immunizing BALC/c mice with HCC SMMC-7721 cells. Solid phase enzyme-linked immunoabsorbent assay (ELISA) analysis showed that this mAb (mAb 95) was reactive with human HCC cell lines and tumor biopsies, but not tumors of other origin or normal tissues tested. Immuno-gold labeling and flow cytometry indicated that mAb 95 bound specifically to HCC cell membrane protein. Western blot analysis showed mAb 95 reacts only with HCC cell lysates, but not with 10 different human normal tissue lysates. The approximate molecular size of the reactive proteins were 40,000 and 60,000 daltons. The specificity of mAb 95 indicates it may be a potential candidate for a targeting agent in HCC immunotherapy or immunodetection.

Animals↗

Mutation in NS5 protein attenuates mouse neurovirulence of yellow fever 17D vaccine virus.

The 17D-204 vaccine manufactured in South Africa (17D-204-SA) and a large plaque variant (17D-LP) derived from it were highly virulent in adult mice. The LD50 of 17D-LP virus was 0-2 p.f.u. for mice following intracerebral inoculation. In comparison, a medium plaque variant derived from 17D-LP, termed 17D-MP virus, was found to be attenuated in adult mice following the same route of inoculation (> 10(4) p.f.u./LD50). Replication of 17D-MP virus was decreased in infected mouse brains compared to 17D-LP virus. Also, 17D-MP virus was slightly temperature sensitive at 39.5 degrees C. Compared to its parent viruses, 17D-204-SA and 17D-LP, 17D-MP virus had one unique mutation at nt 8045 in the genome which resulted in a single amino acid substitution (Pro --> Ser) at residue 137 of the NS5 protein and appeared to be the mutation responsible for the attenuation of 17D-MP virus. This is the first time that altered virulence of a flavivirus caused by mutation in a non-structural protein gene, other than NS1, has been reported.

Amino Acid Sequence↗

EGF receptor regulation of cell motility: EGF induces disassembly of focal adhesions independently of the motility-associated PLCgamma signaling pathway.

A current model of growth factor-induced cell motility invokes integration of diverse biophysical processes required for cell motility, including dynamic formation and disruption of cell/substratum attachments along with extension of membrane protrusions. To define how these biophysical events are actuated by biochemical signaling pathways, we investigate here whether epidermal growth factor (EGF) induces disruption of focal adhesions in fibroblasts. We find that EGF treatment of NR6 fibroblasts presenting full-length WT EGF receptors (EGFR) reduces the fraction of cells presenting focal adhesions from approximately 60% to approximately 30% within 10 minutes. The dose dependency of focal adhesion disassembly mirrors that for EGF-enhanced cell motility, being noted at 0.1 nM EGF. EGFR kinase activity is required as cells expressing two kinase-defective EGFR constructs retain their focal adhesions in the presence of EGF. The short-term (30 minutes) disassembly of focal adhesions is reflected in decreased adhesiveness of EGF-treated cells to substratum. We further examine here known motility-associated pathways to determine whether these contribute to EGF-induced effects. We have previously demonstrated that phospholipase C(gamma) (PLCgamma) activation and mobilization of gelsolin from a plasma membrane-bound state are required for EGFR-mediated cell motility. In contrast, we find here that short-term focal adhesion disassembly is induced by a signaling-restricted truncated EGFR (c'973) which fails to activate PLCgamma or mobilize gelsolin. The PLC inhibitor U73122 has no effect on this process, nor is the actin severing capacity of gelsolin required as EGF treatment reduces focal adhesions in gelsolin-devoid fibroblasts, further supporting the contention that focal adhesion disassembly is signaled by a pathway distinct from that involving PLCgamma. Because both WT and c'973 EGFR activate the erk MAP kinase pathway, we additionally explore here this signaling pathway, not previously associated with growth factor-induced cell motility. Levels of the MEK inhibitor PD98059 that block EGF-induced mitogenesis and MAP kinase phosphorylation also abrogate EGF-induced focal adhesion disassembly and cell motility. In summary, we characterize for the first time the ability of EGFR kinase activity to directly stimulate focal adhesion disassembly and cell/substratum detachment, in relation to its ability to stimulate migration. Furthermore, we propose a model of EGF-induced motogenic cell responses in which the PLCgamma pathway stimulating cell motility is distinct from the MAP kinase-dependent signaling pathway leading to disassembly and reorganization of cell-substratum adhesion.

Animals↗

Establishment of a lymph node metastatic model of mouse hepatocellular carcinoma Hca-F cells in C3H/Hej mice.

To establish a transplantable lymph node metastatic animal model, mouse hepatocellular carcinoma Hca-F cells were implanted into C3H/Hej mice by subcutaneous inoculation. The characters of the metastasis were determined macroscopically and microscopically. During 17 generations, the percentages of metastasis of Hca-F cells remained between 80% and 100%. Hca-F cells metastasized only to the lymph node, and did not disseminate to other organs of C3H/Hej mice. The percentages of metastasis in inoculated mice and the average percentages of lymph node metastasis in each mouse increased in an almost proportional fashion with the number of implanted cells (r = 0.832, for the percentages of metastasis; r= 0.949, for the average percentages of lymph node metastasis) and time after the implantation (r= 0.933, for the percentages of metastasis; r = 0.959, for the average percentages of lymph node metastasis). This transplantable lymph node metastatic model of mouse hepatocellular carcinoma Hca-F cells in C3H/Hej mice provides a useful tool for the study of the mechanism of tumor lymph node metastasis and may provide a new insight into the development of tumor experimental therapy.

Animals↗